These studies will relate alterations in the activity of mitrochondria which result from complete and partial ischemia of the myocardium to the ability of heart cell to recover from these conditions. The responses of isolated heart mitochondria to each of the various conditions associated with ischemia (increased free fatty acid and acyl CoA levels, increased intracellular Ca ion 2, Na ion, lactate, and inorganic phosphate, decreased intracellular pH, and decreased levels of high-energy phosphate, for example), will be defined and conditions sought for restoration of normal mitochondrial activity. A model for myocardial ischemia will be defined using suspensions of isolated adult rat heart cells maintained at increasing concentrations in an anaerobic atmosphere. Viability and recovery curves for these cells will be relatd to their morphology and biochemical properties. The condition of the mitochondria at significant points along the deterioration and recovery curve will be established by compartmental analysis and by isolation of the mitochondria. We will also explore the possibility of using cells confined in a flow-dialysis cell to construct a model for partial ischemia in which a nutrient solution can be delivered at known rates of perfusion. Comparison of the properties of mitochondria isolated from ischemic cells with the various effects determined from the model studies of conditions which damage control mitochondria should help establish the condition of the cells and the mitochondria at the "point of no return" in which cellular deterioration becomes irreversible. Finally, we will determine whether interventions which reverse mitochondrial alterations are also beneficial with respect to the recovery of isolated heart cells from ischemia.